Micro RNA-98 suppresses interleukin-10 in peripheral B cells in patient post-cardio transplantation

// Jiangping Song 1, * , Wenjun Su 1, * , Xiao Chen 1 , Qian Zhao 1 , Ningning Zhang 1 , Mao-Gang Li 2 , Ping-Chang Yang 2 , Liqing Wang 1 1 State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Xicheng District, Beijing, 100037, China 2 The Research Center of Allergy and Immunology, Shenzhen University School of Medicine, Shenzhen, 518060, China * These authors contributed equally to this work Correspondence to: Liqing Wang, email: fwsongjiangping@126.com Keywords: B lymphocyte, interleukin-10, micro RNA, heart transplantation, cortisol Received: September 20, 2016 Accepted: February 28, 2017 Published: March 08, 2017 ABSTRACT The immune tolerance to the transplant heart survival is critical. Regulatory B cells are one of the major immune regulatory cell populations in the immune tolerance. Micro RNAs (miR) can regulate the activities of immune cells, such as the expression of interleukin (IL)-10 by B cells. This study tests a hypothesis that micro RNA (miR)-98 plays a role in the regulation of interleukin (IL)-10 expression in B cells (B10 cell) after heart transplantation. In this study, the peripheral blood samples were collected from patients before and after heart transplantation. The expression of miR-98 and IL-10 in B cells was assessed by real time RT-PCR. An allograft heart transplantation mouse model was developed. We observed that after heart transplantation, the frequency of peripheral B10 cell and the IL-10 mRNA levels in peripheral B cells were significantly decreased, the levels of miR-98 were increased in peripheral B cells and the serum levels of cortisol were increased in the patients. Treating naive B cells with cortisol in the culture suppressed the expression of IL-10 in B cells, which was abolished by knocking down the miR-98 gene. Administration with anti-miR-98, or cortisol inhibitor, or adoptive transfer with B10 cells, significantly enhanced the survival rate and time of mice received allograft heart transplantation. In conclusion, the enhancement of serum cortisol affects the immune tolerant feature of B cells, which can be attenuated by anti-miR-98-carrying liposomes.